We previously reported on the relationship of body composition and radiographic knee osteoarthritis development by analyzing longitudinal data acquired from the participants of the Baltimore Longitudinal Study on Aging (BLSA). Body composition data (fat and lean mass) acquired from 593 dual photon xray absorptiometry (DXA) scans of BLSA participants who had no evidence of knee osteoarthritis (OA) on an initial knee radiograph and underwent a second xray 10 years later. Body weight, and the ratios of fat to lean mass (60.97 versus 51.03 kg; p < 0.01) and fat mass to body weight (36.52 versus 32.43 kg; p < 0.001) were significantly higher in the 41 participants who went on to develop knee OA than those who remained free of radiographic disease in the 10 year observation period. We conducted further analyses to determine whether weight loss reduced the risk of knee OA development in the BLSA cohort. Interestingly, weight loss reduced the risk of knee OA development in men but not in women. We also examined the relationship between bone mineral density (BMD) and knee (OA) in this sample of volunteers. Data from 230 BLSA participants with OA were compared to the 211 who remained free of KOA over a 10-year follow-up interval. Taking age, gender, body mass index (BMI) and time interval between studies into account, BMD was higher with in younger subjects with more advanced OA, and lower in older subjects with advanced OA. The results of these analyses emphasize the complexity of the relationship between OA, body fatness and bone density and underscore the importance of taking age and gender into account. We will be conducting a study to investigate inflammatory, metabolic and hormonal factors mediators of the above reported relationships between body composition (body fatness and bone mineral density) and knee osteoarthritis development, and also to determine these factors respond to weight loss and physical activity. We analyzed data acquired from participants of the Women?s Health and Aging Studies in close collaboration with the Johns Hopkins University?s Center for Aging and Health to delineate the relationship between knee OA and functional limitations. First, we examined the contribution of painful symptoms to the development of severe functional difficulties in already disabled women. Up to 24% of the WHAS I cohort (n=1002) reported widespread pain at baseline. Women with widespread pain were 2.5 to 3.5 times more likely to have severe difficulty with daily activities, walking, or lifting at baseline compared with women who had no or mild pain. In women without severe difficulty initially, widespread pain nearly doubled the risk for progression to severe difficulty in each of the tasks, after adjustment for age, body mass index, comorbid illness, and other confounders. These findings were published last year. We then went on to examine the relationship between knee OA and mobility function in the WHAS II cohort comprised of 436 high functioning older women. Despite their high level of self-reported function, performance was slower and task modification more frequently reported amongst the 117 women with KOA than the 285 women without KOA. These findings imply that mobility function impairment occurs early in knee OA. Furthermore, lower knee extensor strength, higher body weight, and greater pain severity were associated with OA, and also with functional limitations. These results have been accepted for publication.